For X-ray diagnostic testing, for example concerning the organs of the urinary tract and the vessels visualized by angiography, compatible salts of 2,4-6-triiodobenzoic acids have been developed as contrast media. These compounds, however, are not tolerated by the organism without side effects at relatively high dosages, although their toxicity is frequently minor. An adequate visualization of the vascular system, the urinary tract system, as well as the cerebrospinal cavities and other systems requires the use of high dosages of contrast media, or highly concentrated solutions. Consequently, the physicochemical properties of the contrast media and their solutions have high significance. Important pharmacological effects, such as pain, blood pressure declines, vascular damage, and many others are attributed to such properties.
Compared with the salts of triiodinated benzoic acid derivatives, water-soluble nonionic compounds exhibit a series of advantages. For example they have a lower osmotic pressure, thus causing less pain and lesser damage to the endothelium in angiography. Furthermore, their urine concentration is higher and, for subarachnoid injection, arachnoiditis is less frequently encountered. In myelography, a lower tendency toward convulsions (epileptogenicity) has been observed using the nonionic X-ray contrast media. However, it has not been possible to prepare solutions sufficiently concentrated and radiopaque for use in angiography and myelography using these compounds, including, for example, metrizamide or iopamidol, which solutions are not hypertonic with respect to the blood or other body fluid.
Compatible, hexaiodinated and nonionic X-ray contrast media from which highly concentrated and blood-isotonic, aqueous solutions can be prepared were described for the first time in DOS [German Unexamined Laid-Open Application] No. 2,628,517 (U.S. Pat. No. 4,239,747). Similar compounds have also been disclosed in DOS No. 2,805,928 (U.S. Pat. No. 4,139,605).
Although nonionic hexaiodinated X-ray contrast media are rather well compatible on account of their advantageous physicochemical properties (especially strong hydrophilicity and low osmotic pressure), the results attained with the compounds described thus far have not as yet been fully satisfactory. For example, one disadvantage is the high viscosity of precisely the compounds having high compatibility and ready solubility and/or the low solubility of less viscous compounds with a high iodine content, as well as certain toxic effects upon intravenous administration of several of the heretofore disclosed compounds in spite of relatively high LD.sub.50 values.